Distinguishing between models of carcinogenesis: The role of clonal expansion

https://doi.org/10.1016/0272-0590(91)90210-UGet rights and content

Abstract

Several multistage models have been proposed to describe the process of carcinogenesis. The model attributed to Armitage and Doll (1954, Brit. J. Cancer 8, 1–12) assumes that a normal cell is transformed into a malignant cell by k ≥1 fundamental biological events. The model usually attributed to Moolgavkar and colleagues (1979, Math. Biosci. 47, 54–77; 1981, J. Natl. Cancer Inst. 66, 1037–1052) assumes that carcinogenesis is a two-stage process, taking into account the ability of premalignant cells to proliferate. In this paper, we investigate our ability to distinguish between these models using animal carcinogenicity data. Three different approaches are considered: one based on actual tumor incidence data from National Toxicology Program experiments and two based on simulated data. The results show that both models will adequately fit most tumor incidence data. This implies that we must be cautious in accepting the biological basis of either of these models simply because it “fits the data.” Suggestions for experimental designs and toxicological endpoints (other than tumor incidence) which might provide for better discrimination between models are given.

References (40)

  • P.J. Cook et al.

    A mathematical model for the age distribution of cancer in man

    Int. J. Cancer

    (1969)
  • H. Cramer
  • B. Efron
  • L.B. Ellwein et al.

    A cellular dynamics model of experimental bladder cancer: Analysis of the effect of sodium saccharin in the rat

    Risk Anal.

    (1988)
  • E. Farber

    The multistep nature of cancer development

    Cancer Res.

    (1984)
  • R.E. Greenfield et al.

    A general probabilistic model of carcinogenesis: Analysis of experimental urinary bladder cancer

    Carcinogenesis

    (1984)
  • D. Hoel et al.

    The impact of toxicity on carcinogenicity studies: Implications for risk assessment

    Carcinogenesis

    (1988)
  • A. Kopp et al.

    A note on approximating the cumulative distribution function of the time to tumor onset in multistage models

    Biometrics

    (1989)
  • S.H. Moolgavkar et al.

    Two-stage models for carcinogenesis: Epidemiology of breast cancer in females

    J. Natl. Cancer Inst.

    (1980)
  • S.H. Moolgavkar et al.

    Mutation and cancer: A model for human carcinogenesis

    J. Natl. Cancer Inst.

    (1981)
  • Cited by (0)

    View full text